http://www.dietcan.net/docs/Polifenoles%20en%20alimentos%20y%20biodisponibilidad.pdf

Polyphenols: food sources and bioavailability

BET Bromodomain Inhibition as a Therapeutic Strategy to Target c-Myc

Our appreciation of the physiological functions of estrogens and the mechanisms through which estrogens bring about these functions has changed during the past decade. Just as transgenic mice were produced in which estrogen receptors had been inactivated and we thought that we were about to understand the role of estrogen receptors in physiology and pathology, it was found that there was not one but two distinct and functional estrogen receptors, now called ERα and ERβ. Transgenic mice in which each of the receptors or both the receptors are inactive have revealed a much broader role for estrogens in the body than was previously thought. This decade also saw the description of a male patient who had no functional ERα and whose continued bone growth clearly revealed an important function of estrogen in men. The importance of estrogen in both males and females was also demonstrated in the laboratory in transgenic mice in which the aromatase gene was inactivated. Finally, crystal structures of the estrogen r...

Mechanisms of Estrogen Action

The complete title of this book runs ‘Analyzing Linguistic Data: A Practical Introduction to Statistics using R’ and as such it very well reflects the purpose and spirit of the book. The author guides the reader in about 350 pages from descriptive and basic statistical methods over classification and clustering to (generalised) linear and mixed models. Each of the methods is introduced in the context of concrete linguistic problems and demonstrated on exciting datasets from current research in the language sciences. In line with its practical orientation, the book focuses primarily on using the methods and interpreting the results. This implies that the mathematical treatment of the techniques is held at a minimum if not absent from the book. In return, the reader is provided with very detailed explanations on how to conduct the analyses using R [1]. The first chapter sets the tone being a 20-page introduction to R. For this and all subsequent chapters, the R code is intertwined with the chapter text and the datasets and functions used are conveniently packaged in the languageR package that is available on the Comprehensive R Archive Network (CRAN). With this approach, the author has done an excellent job in enabling researchers and students alike to reproduce the analyses and learn by doing. Another quality as a textbook is the fact that every chapter ends with Workbook sections where the user is invited to exercise his or her analysis skills on supplemental datasets. Full solutions including code, results and comments are given in Appendix A (30 pages). Instructors are therefore very well served by this text, although they might want to balance the book with some more mathematical treatment depending on the target audience. After the introductory chapter on R, the book opens on graphical data exploration. Chapter 3 treats probability distributions and common sampling distributions. Under basic statistical methods (Chapter 4), distribution tests and tests on means and variances are covered. Chapter 5 deals with clustering and classification. Strangely enough, the clustering section has material on PCA, factor analysis, correspondence analysis and includes only one subsection on clustering, devoted notably to hierarchical partitioning methods. The classification part deals with decision trees, discriminant analysis and support vector machines. The regression chapter (Chapter 6) treats linear models, generalised linear models, piecewise linear models and a substantial section on models for lexical richness. The final chapter on mixed models is particularly interesting as it is one of the few text book accounts that introduce the reader to using the (innovative) lme4 package of Douglas Bates which implements linear mixed-effects models. Moreover, the case studies included in this

Analyzing linguistic data: a practical introduction to statistics using R

It has been estimated by various authorities that about one-third of cancers in Western high-income societies are attributable to factors relating to food, nutrition and physical activity. Identifying with confidence specific associations between dietary patterns, foods, body composition or individual nutrients is not simple because of the long latent period for cancer development, its complex pathogenesis and the challenge of characterising the multidimensional aspects of diet and activity over a lifetime. Reliable conclusions must therefore be drawn not only from randomised controlled trials but from a variety of methodological approaches, judged within a classic framework for inferring causality. Using a newly-developed method with a protocol for standardising the literature search and for analysis and display of the evidence, nine independent academic centres have conducted systematic reviews addressing the causal associations between food, nutrition and physical activity and risk of development of seventeen cancers, as well as of weight gain and obesity. A review has also examined the efficacy of such interventions in subjects with cancer. The reviews have been assessed by an independent Panel of twenty-one international experts who drew conclusions with grades of confidence in the causality of associations and made recommendations. Recommendations are given as public health goals as well as for individuals.

/pdf/the-second-world-cancer-research-fund-american-institute-for-4wjy2ptzze.pdf

The second World Cancer Research Fund/American Institute for Cancer Research expert report. Food, nutrition, physical activity, and the prevention of cancer: a global perspective.

Network pharmacology applications to map the unexplored target space and therapeutic potential of natural products

The potential for the extraction of the plant lignan hydroxymatairesinol (HMR) in large scale from Norway spruce (Picea abies) has given us the opportunity to study the metabolism and biological actions of HMR in animals. HMR, the most abundant single component of spruce lignans, was metabolized to enterolactone (ENL) as the major metabolite in rats after oral administration. The amounts of urinary ENL increased with the dose of HMR (from 3 to 50 mg/kg), and only minor amounts of unmetabolized HMR isomers and other lignans were found in urine. HMR (15 mg/kg body wt po) given for 51 days decreased the number of growing tumors and increased the proportion of regressing and stabilized tumors in the rat dimethylbenz[a]anthracene-induced mammary tumor model. HMR (50 mg/kg body wt) did not exert estrogenic or antiestrogenic activity in the uterine growth test in immature rats. HMR also showed no antiandrogenic responses in the growth of accessory sex glands in adult male rats. Neither ENL nor enterodi...

Hydroxymatairesinol, a novel enterolactone precursor with antitumor properties from coniferous tree (Picea abies).

Aromatization of androgens is a key step in estrogen production, and it regulates the delicate balance between estrogens and androgens in the gonads and sex steroid target tissues. In the present study, we generated transgenic mice (AROM(+)) bearing the human ubiquitin C promoter/human P450 aromatase fusion gene. AROM(+) male mice are characterized by an imbalance in sex hormone metabolism, resulting in elevated serum E(2) concentrations, combined with significantly reduced testosterone and FSH levels, and elevated levels of PRL and corticosterone. AROM(+) males present a multitude of severe structural and functional alterations in the reproductive organs, such as cryptorchidism associated with Leydig cell hyperplasia, dysmorphic seminiferous tubules, and disrupted spermatogenesis. The males also have small or rudimentary accessory sex glands with abnormal morphology; a prominent prostatic utricle with squamous epithelial metaplasia, and edema in the ejaculatory ducts and vas deferens. In addition, the abdominal muscle wall is thin, and the adrenal glands are enlarged, with cortical hyperplasia. Some of the abnormalities, such as undescended testes and undeveloped prostate, resemble those observed in animals exposed perinatally to high levels of exogenous estrogen, indicating that the elevated aromatase activity results in excessive estrogen exposure during early phases of development. Some of the disorders in the reproductive organs, furthermore, can be explained by the fact that AROM(+) males are hypoandrogenic, and have elevated levels of serum PRL and corticosterone. Thus, the AROM(+) mouse model provides a novel tool to investigate the consequences of a prolonged increase in conversion of androgens to estrogens which results in complex hormonal disturbances altering the structure and function of various male reproductive organs.

/pdf/altered-structure-and-function-of-reproductive-organs-in-4efgjbjezu.pdf

Altered structure and function of reproductive organs in transgenic male mice overexpressing human aromatase.

Review of the existing literature suggests that consumption of soy foods or an exposure to a soy isoflavone genistein during childhood and adolescence in women, and before puberty onset in animals, reduces later mammary cancer risk. In animal studies, an exposure that is limited to the fetal period or adult life does not appear to have the same protective effect. A meta-analysis of human studies indicates a modest reduction in pre- and postmenopausal risk when dietary intakes are assessed during adult life. These findings concur with emerging evidence indicating that timing may be vitally important in determining the effects of various dietary exposures on the susceptibility to develop breast cancer. In this review, we address the mechanisms that might mediate the effects of an early life exposure to genistein on the mammary gland. The focus is on changes in gene expression, such as those involving BRCA1 and PTEN. It will be debated whether mammary stem cells are the targets of genistein-induced alterations and also whether the alterations are epigenetic. We propose that the effects on mammary gland morphology and signalling pathways induced by pubertal exposure to genistein mimic those induced by the oestrogenic environment of early first pregnancy.

/pdf/the-role-of-early-life-genistein-exposures-in-modifying-2e92epc6v6.pdf

The role of early life genistein exposures in modifying breast cancer risk

Lignans are a large group of fiber-associated phenolic compounds widely distributed in edible plants. Some of the ingested plant lignans are converted by intestinal microbiota to enterolignans, enterodiol (END) and enterolactone (ENL), the latter of which has been thought to be the major biologically active lignan, and suggested to be associated with low risk of breast cancer. In line with this, administration of plant lignans which are further metabolized to ENL, or ENL as such, have been shown to inhibit or delay the growth of experimental mammary cancer. The mechanism of anticarcinogenic action of ENL is not yet fully understood, but there is intriguing evidence for ENL as a modulator of estrogen signaling. These findings have generated interest in the use of lignans as components of breast cancer risk reducing functional foods. Identification of target groups, who would benefit most, is of pivotal importance. Therefore, further identification and validation of relevant biomarkers, which can be used as indicators of lignan or ENL action and breast cancer risk reduction at different stages of the disease, are of importance.

Niina Saarinen

Papers

Network pharmacology applications to map the unexplored target space and therapeutic potential of natural products

Hydroxymatairesinol, a novel enterolactone precursor with antitumor properties from coniferous tree (Picea abies).

Altered structure and function of reproductive organs in transgenic male mice overexpressing human aromatase.

The role of early life genistein exposures in modifying breast cancer risk

Role of dietary lignans in the reduction of breast cancer risk.